Guest guest Posted April 30, 2009 Report Share Posted April 30, 2009 CMT 1E and 2F Mutations Neurofilament Mutations: 1E and 2F Thursday ANN Poster Session Seattle Thursday, April 30, 2009 7:00 AM [P07.166] Different Pathologic Features in Neurfilament Light Chain (NEFL) Pro22 Mutation in Charcot-Marie-Tooth Disease Ji Soo Shin, Sooyeoun You, Sun Young Cho, Su Jin Hwang, Kee-Duk Park, Kyoung-Gyu Choi, Byung-Ok Choi, Seoul, Republic of Korea OBJECTIVE: In this present study we identified and NEFL Pro22Arg mutation in a Korean CMT1F family and investigated the presentation and pathologic features in comparison with previously reported Pro22 muatations. BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a form of hereditary neuropathy. Mutations in the NEFL gene are present in CMT2E and CMT1F neuropathies. Two NEFL gene mutations in the Pro22 locus have been reported. The possibility that mutation in Pro22 in the head domain of the NEFL gene abolishes the Thr-Pro phosphorylation sequence in this area by proline-directed protein kinases has been suggested. DESIGN/METHODS: Two patients with NEFL Pro22Arg mutations in a Korean CMT1F family were identified. The two patients' (mother and son) clinical manifestations of progressive neuropathy as well as electrophysiologic and histopathologic findings were studied. RESULTS: The proband(F/41) complained of progressive gait difficulty and lower limb weakness. She first experienced gait difficulty at 13 years of age. Neurological examination at 41 years revealsed distal wasting and muscle weakness in the lower limbs and both hands, with proximal thigh muscle invovement. Vibration and pain perception was reduced in the distal limbs, and all muscle stretch relfexes were absent. All nerve action potentials were undetectable. Histopathological evaluation revealed onion bulb formations but no giant axons. The son of the patient (M/16) began to experience progressive gait abnormalities at 3 years of age. Neurological examination revealed moderate weakness and atrophy of distal muscles. All sensory modailites showed impairment in the distal parts of the extremities. Stretch reflexes were absent. Nerve conduction studies were consistent with demyelinating neuropathy. CONCLUSIONS/RELEVANCE: The clinical and pathological characteristics defined patients with Pro22Arg mutations reveal its association with demyelinating neuropathy features in CMT1F. It appears that the Pro22 mutations may influence not only the Thr-Pro phosphorylation site by proline-directed protein kinases, but also may induce additional stuctural alteraation of the NEFL protein. Quote Link to comment Share on other sites More sharing options...
Recommended Posts
Join the conversation
You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.